Format

Send to

Choose Destination
Cell Metab. 2018 Dec 4;28(6):922-934.e4. doi: 10.1016/j.cmet.2018.08.003. Epub 2018 Aug 30.

Insulin Receptor-Mediated Stimulation Boosts T Cell Immunity during Inflammation and Infection.

Author information

1
Division of Cellular & Molecular Biology, Diabetes Research Group, Toronto General Research Institute (TGRI), University Health Network, 101 College Street, Toronto, ON M5G 1L7, Canada. Electronic address: stsai@uhnresearch.ca.
2
Division of Cellular & Molecular Biology, Diabetes Research Group, Toronto General Research Institute (TGRI), University Health Network, 101 College Street, Toronto, ON M5G 1L7, Canada.
3
Department of Immunology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
4
Division of Cellular & Molecular Biology, Diabetes Research Group, Toronto General Research Institute (TGRI), University Health Network, 101 College Street, Toronto, ON M5G 1L7, Canada; Department of Immunology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
5
Department of Pathology, Stanford University, Palo Alto, CA, USA.
6
Division of Cellular & Molecular Biology, Diabetes Research Group, Toronto General Research Institute (TGRI), University Health Network, 101 College Street, Toronto, ON M5G 1L7, Canada; Department of Immunology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Division of Endocrinology and Metabolism, Department of Medicine, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, ON M5S 1A8, Canada; Toronto General Research Institute (TGRI), Toronto, ON M5G 2C4, Canada.
7
Department of Immunology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Toronto General Research Institute (TGRI), Toronto, ON M5G 2C4, Canada.
8
Division of Cellular & Molecular Biology, Diabetes Research Group, Toronto General Research Institute (TGRI), University Health Network, 101 College Street, Toronto, ON M5G 1L7, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Department of Laboratory Medicine, St. Michael's Hospital, Toronto, ON M5B 1W8, Canada.
9
Division of Cellular & Molecular Biology, Diabetes Research Group, Toronto General Research Institute (TGRI), University Health Network, 101 College Street, Toronto, ON M5G 1L7, Canada; Department of Immunology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Department of Pathology, University Health Network, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Toronto General Research Institute (TGRI), Toronto, ON M5G 2C4, Canada. Electronic address: dan.winer@uhn.ca.

Abstract

T cells represent a critical effector of cell-mediated immunity. Activated T cells engage in metabolic reprogramming during effector differentiation to accommodate dynamic changes in energy demands. Here, we show that the hormone, insulin, and downstream signaling through its insulin receptor shape adaptive immune function through modulating T cell metabolism. T cells lacking insulin receptor expression (LckCre+ Insrfl/fl) show reduced antigen-specific proliferation and compromised production of pro-inflammatory cytokines. In vivo, T cell-specific insulin receptor deficiency reduces T cell-driven colonic inflammation. In a model of severe influenza infection with A/PR8 (H1N1), lack of insulin receptor on T cells curtails antigen-specific immunity to influenza viral antigens. Mechanistically, insulin receptor signaling reinforces a metabolic program that supports T cell nutrient uptake and associated glycolytic and respiratory capacities. These data highlight insulin receptor signaling as an important node integrating immunometabolic pathways to drive optimal T cell effector function in health and disease.

KEYWORDS:

T cell function; T cell metabolism; adaptive immunity; anti-viral immunity; insulin; insulin resistance; obesity

PMID:
30174303
DOI:
10.1016/j.cmet.2018.08.003

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center